Ferric Citrate for the Prevention of Renal Failure in Adults With Advanced Chronic Kidney Disease (FRONTIER)

Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Determine the Effect of Ferric Citrate on Time to a Composite Endpoint of Initiation of Maintenance Dialysis or All-cause Mortality vs Placebo in Adults With Advanced CKD

A 9-month randomized, double-blind, placebo-controlled study to compare the effect of fixed dose ferric citrate versus placebo in patients with advanced chronic kidney disease (eGFR ≤20 ml/min/1.73m2) on the composite endpoint of time to initiation of maintenance dialysis or all-cause mortality.

Study Overview

• Status: Completed
• Conditions: Disease Progression; Renal Insufficiency, Chronic; Hyperphosphatemia; Anemia, Iron Deficiency; Renal Anemia; Iron; Cardiovascular
• Intervention / Treatment: Drug: Ferric Citrate 1 GM Oral Tablet [AURYXIA]; Drug: Placebo

Detailed Description

This multicenter, randomized, double-blind, placebo-controlled clinical trial is being conducted to determine the effect of ferric citrate on the time to a composite endpoint of initiation of maintenance dialysis or all-cause mortality in patients with non-dialysis dependent, advanced CKD. Up to 400 subjects will be randomized in 1:1 ratio to receive either ferric citrate or matching placebo. All subjects will initiate dosing at 2 tablets per meal or snacks, up to 3 times per day (maximum of 6 tablets per day). The dose of ferric citrate/placebo will only be adjusted based on safety and/or tolerability. Given the double-blind design of this trial, investigators will be instructed to not prescribe commercial Auryxia to either study arm. Study visits during the treatment period are to be conducted as part of routine scheduled clinical encounters. Standard of care local laboratory results will be collected however no study specific laboratory tests other than a pregnancy test in women of child-bearing potential will be required.

• Study Type: Interventional
• Enrollment (Actual): 289
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Pine Bluff, Arkansas, United States, 71603
      • Arkansas Nephrology & Hypertension Clinic
  • California
    • Chula Vista, California, United States, 91910
      • Balboa Research SMO
    • El Centro, California, United States, 92243
      • Balboa Research SMO
    • Escondido, California, United States, 92025
      • Balboa Research SMO
    • La Mesa, California, United States, 91942
      • Balboa Research SMO
    • San Diego, California, United States, 92111
      • Balboa Research SMO - Kearney Mesa
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Kidney Care
  • Florida
    • Fort Myers, Florida, United States, 33908
      • Associates in Nephrology
  • Georgia
    • Albany, Georgia, United States, 31701
      • Dialysis Clinic, Inc.
    • Dalton, Georgia, United States, 30720
      • Nephrology and Hypertension Specialists, PC
  • Indiana
    • Shelbyville, Indiana, United States, 46176
      • Major Health Partners
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kidney Associates of Kansas City
  • New Jersey
    • South River, New Jersey, United States, 08882
      • Nephrology-Hypertension Associates of Central NJ
  • New Mexico
    • Gallup, New Mexico, United States, 87301
      • High Desert Nephrology Associates
  • New York
    • Amherst, New York, United States, 14228
      • Nephrology Associates of Western NY
  • South Carolina
    • Spartanburg, South Carolina, United States, 29302
      • Spartanburg Nephrology Associates
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Dialysis Clinic, Inc.
  • Texas
    • Live Oak, Texas, United States, 78233
      • South Texas Renal Care Group
    • San Antonio, Texas, United States, 78212
      • Clinical Advancement Center, PLLC
    • San Antonio, Texas, United States, 78202
      • South Texas Renal Care Group
    • San Antonio, Texas, United States, 78211
      • South Texas Renal Care Group
    • San Antonio, Texas, United States, 78221
      • South Texas Renal Care Group
    • San Antonio, Texas, United States, 78251
      • South Texas Renal Care Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult patients greater or equal to 18 years old.
2. Diagnosis of NDD advanced CKD, regardless of etiology. Advanced CKD is defined as at least one local laboratory determined estimated glomerular filtration rate (eGFR) ≤20 ml/min/1.73m2 (calculated per any commonly used method or equation for estimating eGFR) within 90 days of Day 1.
3. Most recent transferrin saturation (TSAT) less than or equal to 45% within 45 days of Day 1.
4. Most recent serum phosphate is greater or equal to 3.0 mg per dL within 45 days of Day 1.
5. Most recent ferritin is less than or equal to 500 ng per mL within 45 days of Day 1.
6. Women of child-bearing potential must have a negative serum or urine pregnancy test within 28 days prior to Day 1.
7. Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure.

Exclusion Criteria:

1. Patients who, in the opinion of the Investigator, have acute kidney injury rather than CKD.
2. Patients with planned/imminent maintenance dialysis, or that are anticipated to begin maintenance dialysis within 8 weeks from Screening, in the opinion of the Investigator.
3. A known allergy or intolerance to ferric citrate or any of its constituents.
4. Hypersensitivity reaction to previous oral iron therapy.
5. History of hemochromatosis or iron overload syndrome (e.g., hereditary sideroblastic anemia, thalassemia, polycythemia vera).
6. Active malignancy requiring current treatment except for non-melanoma skin cancer regardless of treatment.
7. Active drug or alcohol dependence or abuse (excluding tobacco use or use of medical or recreational marijuana) within the 12 months prior to Screening or evidence of such abuse, in the opinion of the Investigator.
8. Limited life expectancy (less than 6 months) in the opinion of the Investigator.
9. Females who are known to be pregnant or are breast-feeding during Screening or are planning to become pregnant and breastfeeding during the study period.
10. Evidence of a clinically active infection requiring antibiotics at Randomization.
11. Unable to comply with study requirements or in the opinion of the Investigator, not clinically stable to participate in the study.
12. Use of an investigational medication or participation in an investigational study within 30 days prior to Day 1.
13. Patients with a scheduled date for receipt of living donor kidney transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ferric citrate; Supplied as tablets for oral administration containing 1 gram ferric citrate (210 milligrams of ferric iron). Administered orally with meals or snacks.	Drug: Ferric Citrate 1 GM Oral Tablet [AURYXIA]; All subjects will be instructed to take study drug (ferric citrate or placebo) at a fixed dose of 2 tablets per meal or snacks, up to three times per day. The maximum dose is 6 tablets per day. No additional tablets (beyond a total of 6 per day) should be taken. Tablets should not be crushed or chewed.; Other Names: Auryxia
Placebo Comparator: Placebo; Tablets, matching in color and size to ferric citrate.	Drug: Placebo; All subjects will be instructed to take study drug (ferric citrate or placebo) at a fixed dose of 2 tablets per meal or snacks, up to three times per day. The maximum dose is 6 tablets per day. No additional tablets (beyond a total of 6 per day) should be taken. Tablets should not be crushed or chewed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Achieving a Composite Endpoint of Initiation of Maintenance Dialysis or All-cause Mortality	Number of participants achieving a composite endpoint of initiation of maintenance dialysis or all-cause mortality	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization Events Reported as a Serious Adverse Event (SAE) (Excluding Disease-related Hospitalization [e.g., Dialysis Access Placement, Dialysis Initiation, Kidney Transplant] and Elective Procedures)	Number of hospitalization events reported as a serious adverse event (SAE) (excluding disease-related hospitalization [e.g., dialysis access placement, dialysis initiation, kidney transplant] and elective procedures)	9 months
Component of Primary - Initiation of Maintenance Dialysis	Component of Primary - Number of participants initiating maintenance dialysis	9 months
Component of Primary - All-Cause Mortality	Component of Primary - Number of patients reaching endpoint of all-cause mortality.	9 months

Collaborators and Investigators

• Sponsor: USRC Kidney Research
• Collaborators: Akebia Therapeutics
• Investigators: Principal Investigator: Geoff Block, MD, USRC Kidney Research

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2022
• Primary Completion (Actual): January 24, 2024
• Study Completion (Actual): January 24, 2024

Study Registration Dates

• First Submitted: October 6, 2021
• First Submitted That Met QC Criteria: October 6, 2021
• First Posted (Actual): October 20, 2021

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: ferric citrate
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Hematologic Diseases; Renal Insufficiency; Phosphorus Metabolism Disorders; Anemia; Iron Metabolism Disorders; Anemia, Hypochromic; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Disease Progression; Renal Insufficiency, Chronic; Anemia, Iron-Deficiency; Hyperphosphatemia; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs; ferric citrate
• Other Study ID Numbers: USRC-2021-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No